The Renal Association, October 25, 1978, London, England

Kidney International, Vol. 15 (/979), pp. 445-453

Abstracts The Renal Association London, England October 25, 1978 A study of plasma renin activity and sodium excretion in normotensive subjects with a previous history of estrogen- or preg-

with pretreatment control values in the same animals): 24 hr

McGale, C. Stewart, and G. M. Aber. Renal Research Laboratory, Department of Nephrology, North Staffordshire Hospital Centre, Stoke-on-Trent, England. In view of the similar structural and hemodynarnic abnormalities of the intrarenal circulation noted in patients with a previous history of either estrogen- or

cretion remained essentially unchanged. Marked increases in

nancy-associated hypertension. A. A. Al-Khader, E. H. F.

pregnancy-associated hypertension, the present investigation was designed to study PRA in the supine position, after adopting an upright posture and after acute and "chronic" sodium depletion induced by a single dose of frusemide (1 mg/kg body weight) and I week's treatment with bendrofluazide (5 mg/day), respectively, in similar groups of patients. The natriuretic effect of an i.v. infusion of isotonic saline (300 mmoles in 1 hour) was also studied. Ten patients with a previous history of estrogen-associated hypertension and six with a history of pregnancy-associated hypertension were studied. All were normotensive at the time of study, and none were taking any therapy likely to influence blood pressure, sodium balance, or PRA. The results were compared with those of a control group of 11 subjects, matched for age and parity. The results demonstrate: (1) Low PRA in the supine posi-

tion occurred with an exaggerated rise on adopting an upright posture. (2) An increase in PRA occurred in response to both a single dose of frusemide and after a week's treatment with bendrofluazide, both changes being significantly greater than that seen in the control group (P < 0.05). (3) The increase in PRA induced by bendrofluazide was associated with significantly greater reductions in both body weight (P < 0.05) and plasma

potassium (P < 0.05) than were observed in the control subjects. (4) An exaggerated natriuresis was noted following the i.v. infusion of isotonic saline, in association with a diminished degree of renin suppression compared with controls. The results summarized above were common to both groups of patients studied. They suggest that normotensive patients with a previous history of estrogen- or pregnancy-associated hypertension have disturbances of PRA resulting from abnormalities of sodium conservation and/or volume perception. The exaggerated natriuresis associated with an infusion of isotonic saline in these normotensive subjects is similar to that reported in patients with established hypertension. The available data do not preclude the possibility that such disturbances of PRA and sodium excretion may have actually antedated the complicated pregnancy or the use of estrogen compounds.

urine flow rate increased about two-fold, urinary protein and potassium excretion increased twofold to threefold, but sodium ex-

blood urea nitrogen have also been reported with G administration over a similar time course. Acute studies were performed on the same group of rats on day 15 of G administration and were compared with those carried out on a normal, weight-matched control group of 5 animals. Whole kidney GFR was profoundly 0.03 mlImin compared with reduced in rats given G (0.35 0.95 0.09 mI/mm in controls; P < 0.001). Renal plasma flow (RPF) and whole kidney filtration fraction (FF) were both significantly lower in rats given G compared with controls (1.59 0.25 vs. 2.92 0.43 mllmin, P < 0.025; and 0.24 0.02 vs. 0.32 0.02, P < 0.05, respectively). Despite the reduced GFR in the treated group, urine flow rate was significantly elevated compared with controls (0.0046 0.0009 vs. 0.0018 0.0002 mLlmin; P < 0.025). Rats given G had significantly lower urine to plasma 17 vs. 533 inulin ratios (93 45; P < 0.001), indicating markedly impaired urinary concentrating ability. Thus, administration of this dose of 0 to the rat results in a nonoliguric form of acute renal failure. The decline in GFR observed is due in part to the observed fall in RPF, since in the rat, GFR is highly dependent on RPF. The concomitant decline in FF with G, however, indicates additional impairment of one or more of the other determinants of glomerular ultrafiltration. It is probable that a fall in the glomerular capillary ultrafiltration coefficient, Kf (the product of available filtration surface area and the water permeability of the glomerulus), is the other major determinant of the reduced GFR seen with G, since even very low doses in this same strain of rat result in a maximal reduction of Kf to about 50% of normal. The precise manner in which G (and possibly other nephrotoxic antibiotics as well) evokes these falls in K and RPF remains to be defined. Role of the kidney in silicon metabolism in man. J. W. Dobbie,

M. J. B. Gray, and A. C. Kennedy. Tenovus Kidney Diseases Research Unit, Royal Infirmary, Glasgow, Scotland. Absorption

and urinary excretion of silicon (S) in health and varying degrees of renal impairment were determined in 1,000 subjects. S con-

centration in body fluids was measured by atomic absorption spectroscopy. Initial studies established that in health the kidney is the main excretory organ for absorbed dietary S. Studies on 30 patients with exteriorized biliary secretion failed to demonstrate

any significant enterohepatic circulation of S. Little variation was found in serum S in healthy adults (mean, 0.6 pg/mI; SD, 0.15; N 173). In 240 patients with renal disease, a progressive fall in 24-hour urinary excretion of S occurred with decreasing creatinine clearance. Serum S of patients on hemodialysis was

Mechanism involved in gentamicin-induced acute renal failure. C. Baylis. Department of Physiology, University of Manchester, Manchester, England. Recent observations suggest that the aminoglycoside antibiotic gentamicin (G) exerts nephrotoxic side effects in both man and experimental animals. To define the nature and possible causes of the impairment in renal function following G administration, the present studies were performed on the Munich-Wistar rat, given the drug at a dose of 60 mg/kg body weight per day for 14 days. During the course of chronic G administration to 8 rats the following changes occurred (compared

twice that of normal controls (mean, 1.2 pg/mI; SD, 0.3; N = 40). Following transplantation, serum S tended to fall (mean, 1.0 pg/ ml; so, 0.15; N = 30). Prehemodialysis and posthemodialysis serum S showed a mean fall of 28% in 18 patients after 5 hours' dialysis. This study has shown that urinary S excretion is dependent on dietary intake and renal function, that serum S rises with

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Abstracts

increasing uremia, and that serum S is dialyzable. These findings may, therefore, be of relevance in renal osteodystrophy in view of recent claims that S is an essential element in bone formation.

fluence, which is independent of PN, could represent the combined effect of a number of variables on UNV through changes induced in postglomerular plasma protein concentration.

Renal vein renin measurements in normotensive children. K. G.

Rhythms in renal allograft rejection. Martin S. Knapp, J. R. Cove-Smith, and R. Pownall. Renal Unit, City Hospital, Nottingham, England. Rhythmicity occurs in many biologic events. The frequencies of these rhythms vary from seconds to years,

Gerdts, Vanita Shah, J. M. Savage, and M. J. Dillon. Renal Unit, The Hospital for Sick Children, Great Ormond Street, London, England. Determination of bilateral renal venous renin levels has been established as an important diagnostic procedure to identify surgically curable forms of hypertension in adults and children. However, the interpretation of renal vein renin data is hampered by a lack of information on normal subjects. The defi-

nition of a significant renal vein renin ratio, i.e., the minimum ratio of plasma renin from the affected (R) over that from the contralateral kidney (Rc) clearly identifying pathologic lateralization, remains arbitrary. In an attempt to establish a reference

range for renal venous PRA ratios, we have measured renal venous and caudal inferior vena caval (P) PRA in 49 normoten-

sive children free from renal disease who underwent cardiac catheterization to elucidate their congenital heart lesions. PRA was determined by radioimmunoassay of generated angiotensin 1. There was no significant difference between PRA levels in the renal veins (Student's t = 1.32, P < 0.2). Renal venous PRA was found to be significantly higher than PRA in the inferior vena cava (t = 10, P << 0.001). As in studies on hypertensive subjects, we calculated RJRc by dividing the higher renal venous PRA (R) by the value obtained from the contralateral kidney (Rc), and Re/P correspondingly. A wide variation of Re/P was observed, with a mean of 1.15 (95% confidence limits, 0.78 to 1.62). Four patients had a renal venous PRA that was at the 95% probability level lower than PRA in the inferior vena cava. The possibility of net renin removal by these kidneys is discussed. We found a mean RJRc of 1.16. Three patients had an R/Rc of greater than 1.4, the highest value observed being 1.55. These results support 1.5, the ratio at present most widely accepted for clinical practice, as the upper limit of normality for the interpretation of renal vein renin measurements. Analytical techniques applied to the study of sodium excretion in

dogs. D. Gordon, F. S. Nashat, and C. S. Wilcox. Medical Unit, St. Mary's Hospital Medical School, London, and Department of Physiology, Middlesex Hospital Medical School, London, Eng-

land. The renal excretion of sodium (UNV) was studied in anesthetised dogs during acute changes in plasma sodium concentration (P) induced by infusion of sodium chloride solutions of varying concentration through a needle in the renal artery. Certain other variables known to be capable of influencing UNOV

were also recorded. Principal factor analysis with iteration, followed by varimax rotation, defined four "factors," linear func-

tions of the primary variables, that described the inter-

but most reports in medicine have been concerned with circadian rhythms with a frequency of around 24 hours. We have recently described circadian rhythmicity in cell-mediated immune processes, and have suggested that there may be a circadian variation in events associated with renal allograft rejection in man. A

recent report has suggested that renal allograft rejection may show a 6 to 8 day rhythm. The records of 52 patients who had received a renal transplant, and had been followed with daily plasma creatinine estimations for up to 60 days, were analyzed with plots of the weight-corrected reciprocal of plasma creatinine against time. This method identifies the time when renal function

changes from an improving or stable state to one of deterioration, usually due to allograft rejection. Acute changes in function, not due to obstruction or other complications, were classified as either possible, probable, or certain rejection episodes. The day on which renal function first caused a change in plasma creatinine, not anticipated by the previous sequence of results, was considered to be the "day of rejection." Data from the first 35 transplant patients reviewed in detail included 22 incidents considered to be "certain" rejection. In these episodes, the lines of improving and deteriorating plasma creatinine, expressed as the reciprocal and analyzed by linear regression, showed correlation coefficients greater than 0.8. These lines, when extrapolated, met at an acute angle, with the point of intercept indicating the time when rejection may first have affected creatinine clearance. Such episodes appeared to be more frequent at night than in the day, and it is suggested that there is a circadian rhythm in the timing of rejection (P < 0.01). When the whole series of 52 patients was considered, the most frequent interval observed between the days of "rejection," i.e., the day of onset of decreasing function, was 7 days. We were unable to confirm the suggestion that rejection was most common around the 7th, 14th, 21st, and 28th days posttransplant, but we did note that the most likely day for a first rejection episode was between 6 and 8 days after plasma creatinine had begun to fall, and we suggest that any 7day rhythm may be timed from the onset of function rather than from the day of graft insertion. In summary, a circadian rhythm in renal allograft "rejection" has been demonstrated. A circaseptan ("around 7-day") rhythm in allograft rejection may also be present. Consideration of these rhythms might permit the design of therapeutic regimes that are either more effective or less toxic,

or both.

relationships of the primary variables. The aim was to find dis-

crete sets of strongly intercorrelated variables which could reveal physiologic processes related to UNaV. Factor 1 was strongly correlated with UaV and PNa its other correlations described the acidosis and hypoproteinemia of hypernatremia. Factor 2 was negatively correlated with UNaV. Its correlations with plasma protein concentration, GFR, renal plasma flow, hematocrit, and blood pressure were such as to imply that it represented postglomerular plasma protein concentration and its influence on sodium reabsorption from the tubule. Factors 3 and 4 showed interrelationships of the variables independent Of UNaV. Multiple regression analysis with UNaV as the dependent variable and on-

ly Factors 1 and 2 as independent variables gave an equation with multiple r = 0.74. This explained almost as much of the change in UNaV as an equation with all the primary variables expressed individually (r 0.75). Thus, factor analysis clarified the interpretation of the results of these experiments without loss of descriptive power. The main influence on UNaV was PNa, this requiring, for its full expression, concomitant changes in plasma concentrations of hydrogen ion and protein. The other prime in-

Plasma level and renal clearance of oxalate in normal subjects and in patients with primary hyperoxaluria and/or chronic renal failure. P. O'Regan, A. M. Joekes, A. R. Constable, G. P. Ka-

sidas, and G. Alan Rose. St. Peter's Group of Hospitals and Institute of Urology, London, England. Plasma oxalate has been measured by two different methods. One method is isotopic and applicable at all levels of plasma oxalate and renal function. The other method is enzymatic and only applicable at raised levels of plasma oxalate. Oxalate clearance and the exchangeable oxalate pool were also measured. The radionuclide method was applied to 6 normal volunteers, to 10 patients with chronic renal failure,

to 3 patients who were calcium oxalate stone-formers with idiopathic hypercalciuria and slightly elevated urinary oxalate excretion but a normal glycollic acid excretion, and to 7 patients with primary hyperoxaluria. Some of the latter group were studied at different stages of treatment, i.e., before and after pyridoxme, and before and after transplantation. One hyperoxaluric patient who was the recipient of a successful renal transplant was studied in detail. In 8 patients whose plasma oxalate was greater

Abstracts than 20 moles/liter, the derived isotopic and direct enzymatic measurements of plasma oxalate were carried out. Where the isotopic and the enzymatic methods could be applied simultaneously, the correlation was good. Raised plasma oxalate and raised exchangeable oxalate pool were attributable to both primary hyperoxaluria and chronic renal failure and were seen also in the 3 stone-formers, who were assumed to be intestinal hyperabsorbers of oxalic acid, but for any given creatinine clearance the plasma oxalate and exchangeable oxalate pool were set considerably higher with primary hyperoxaluria than they were with the other conditions. In most normal subjects and most patients, the ratio of clearance of oxalate to clearance of creatinine was greater than 1. Effect of prostacyclin on platelets in hemodialysis: Dialysis without anticoagulation. H. F. Woods, M. J. Weston, and S. Bunting.

Renal Unit, King's College Hospital, London, and Weilcome Research Laboratories, Beckenham, Kent, England. Prostacydin, produced by vascular endothelium, is the most potent inhib-

447

itor of platelet function known to man. To assess its effects on platelet-foreign-surface interactions during hemodialysis, 10 greyhounds were dialyzed with Cuprophan coils (Travenol) and standard dialysis equipment for 90 mm. At the end of dialysis, arterial platelet counts (% of initial) in 5 dogs in which prostacydin had been infused (115.7 8.6) were significantly higher than in 5 animals in which heparin alone was given (77.8 16.8) (P < 0.05). Prostacyclin reduced the extraction of platelets by the dialyzer. The screen filtration pressure of blood leaving the dialyzer, a measurement of platelet aggregates and microemboli, was

not elevated in the animals which received prostacyclin (80

11.3

mm Hg) but rose significantly in those which received

57 mm Hg) (P < 0.02). In another 5 heparin only (249 greyhounds infused with prostacyclin, but which received no

heparin, dialysis was completed without significant clotting within the dialyzer or lines. The platelet count did not fall, the screen filtration pressure did not rise, and tests of blood clotting were not altered compared with predialysis values. Thus prostacyclin

prevents platelet activation during hemodialysis and enables dialysis to be carried out without anticoagulation.

French Society of Nephrology

Paris, France October 21, 1978 Angiography of arteriovenous hemodialysis fistulas. P. Aubert,

A. Bernard, J. Bachet, P. Quentric, B. Goudot, and J. Guédon. C.M.C. Foch 40, Suresnes, France. During the past 5 years, 60 angiographies of hemodialysis arteriovenous fistulas (AAF) were performed on 32 patients. Three methods were used: retrograde

catheterization through femoral artery (3 cases), direct arterial cannulation (6 cases), and retrograde venography (51 cases). Indications for AAF included insufficient blood flow during dialysis

or poor development of the fistula (30 cases), abnormal return pressure of the blood during hemodialysis (16 cases), and others (14 cases). Roentgenographic abnormalities were found in 86.7% of AAF, which was correlated well with clinical findings in 73%. Reliable diagnosis was impossible in 8.3% of AAF, mainly because of inadequate methods, and 5% appeared normal. Roentgenographic findings identified vascular stenosis (56%) or thrombosis (16%), aneurysms (19%), and miscellaneous (9%). AAF was useful for planning appropriate medical or surgical treatment

in 58% of the studies; in 42%, radiologic abnormalities were thought to be compatible with prolonged survival of the fistula, and no treatment was performed. Retrograde venography seems the method of choice for AAF because it is safe and effective in most cases. Urinary lactic deshydrogenase isoenzyme 5 (LDH5) and urinary tract infection in children. F. Bouissou, P. Barthe, J. P. Thouvenot, P. Bourely. Service de Médecine Infantile C, Laboratoire de Biochimie II, Hôpital Purpan, Cedex, France. It has been stated that an increase in urinary excretion of LDH5 is helpful in topographic diagnosis of urinary tract infection (UTI). Sixty-three children (mean age, 6 years) with significant UTI were studied. They had a significantly higher (P < 0.01) LDH5 excretion than control subjects free of UTI had (65 normal children, 32 with renal failure, 29 with the nephrotic syndrome, 88 with uropathy). The presence of renal failure did not influence the results. A good correlation was found with inflammatory tests, quantitative bac-

teriologic count, and leucocyturia. No correlation was found

with immunologic parameters (antibody-coated bacteria in urine, and serum antibodies). According to the results of the preceding

tests and to the presence or not of malformative uropathy, a quantitative score was attributed to each patient. We found a significantly (P < 0.02) higher urinary elimination of LDH5 in patients with high scores (renal infection) than in those with low scores (bladder infection). We conclude that high urinary LDH5 level does not reflect only renal parenchymal infection. LDFI5 excretion may increase with leucocyturia. Itis only a presumptive test, among other techniques, for topographic diagnosis of UTI. These results conflict with previous data obtained in adult patients. Theophylline influence on the ferritin pathway through the gb-

merular basement membrane in the rat. J. Cambar and P. Gendre. Department of Physiology, U.E.R. of Pharmaceutical Sciences, Bordeaux, France. The present study compares the ferritin particle density (particle number/cm2 of micrographic area) within the capillary lumen and the glomerular basement membrane (GBM) in rats infused either with isotonic saline solution (0.15 mlImin flow) (control) or with a 3 mg/mI theophylline solution (treated). Particle density within the capillary lumen was 25.27 3.93 part./cm2 in control rats and 7.7 2.87 after theophylline infusion (— 228%). Within the GBM, particle density was 4.68 1.85 part./cm2 in the control rats, whereas it was 17.11 3.9 in the treated animals (+ 265%). Ferritin density increase within the GBM indicates an augmentation in the proteic

tracer passage through the glomerular barrier. This interpretation is confirmed by the parallel decrease in particle density within the capillary lumen. Many data, which we have recently described, contribute to explaining the present observations. Indeed, we have demonstrated that theophylline, as a cyclic AMP phosphodiesterase inhibitor, increases afferent arteriole diameter and isolated glomeruli diameter, probably by myorelaxant effect on smooth muscle fibers, thus increasing the cortical blood flow. Morphometric ultrastructural studies have confirmed diam-